This is the first time gene therapy has been tested to fight Parkinson's, which affects an estimated 500,000 Americans. The promising findings, published this week in The Lancet, opens the door to a new treatment option for the neurodegenerative disease.

"The safety and effectiveness clearly indicate that this is something worth pursuing," says lead study author Michael Kaplitt, a neurological surgeon and director of movement disorders at New York-Presbyterian Hospital/Weill Cornell Medical Center. "We're not finished, clearly; we still need to do a larger, more definitive study to prove this for sure."

Parkinson's disease, a disorder that typically strikes people in their 60s, is characterized by tremors, stiffness, loss of speech and difficulty with motor function. Neuroscientists have tracked its biological cause to the loss of neurons, or nerve cells, in a midbrain region called the substantia nigra, which produces the neurotransmitter dopamine (that helps maintain proper movement control). When dopamine levels are low the subthalamic nucleus, a sliver of neurons just above the substantia nigra, overproduces glutamate, which is the brain's primary excitatory chemical messenger. When hyped up it overstimulates downstream neurons, triggering a strong inhibitory response that results in disrupted movement.

Kaplitt and senior study author Matthew During, a senior research associate at Weill Cornell, focused on trying to calm down the overactive subthalamic nucleus. They used a harmless virus called an adeno-associated virus to transport a gene that codes for the enzyme glutamic acid decarboxylase (GAD) into the neurons of the subthalamic nucleus. The gene prompted these subthalamic cells to produce gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, which made them settle down and restored normal motor function.

Because of federal regulations, the team could only inject the virus into one hemisphere of each person's brain. "This allowed us to compare the two sides of the brain," Kaplitt says, which enabled researchers to judge the effectiveness of their treatment.

Researchers monitored the 12 subjects over the next year and discovered that motor function improved from 25 percent to 65 percent. They also found that the treated sides of the brain showed normalized brain activity in key regions downstream from the subthalamic nucleus: the thalamus, also implicated in motor function, and parts of the cerebral cortex involved in movement. Most encouraging to the scientists was that the improvement persisted even when the patients were on their Parkinson's medications meaning that, as Kaplitt describes, "the therapy was causing additional improvement to the medicines."

Kaplitt and During had a number of safety concerns at the study's inception: The viral packages could damage target cells by provoking the immune system; there was a chance of overinhibition of the neurons in the subthalamic nucleus; and there were worries about unknown side effects that the researchers had not anticipated. But Kaplitt reports their fears were unfounded—there were no incidents of infection, immune response or toxicity.

In an editorial accompanying The Lancet article, Jon Stoessl, a professor of neurology at Pacific Parkinson's Research Center in Vancouver, calls the new work a "provocative approach to the treatment of neurodegenerative disease." He questions, however, whether this is a better treatment option than deep-brain stimulation, the most effective current therapy, which involves implanting a brain "pacemaker" to electrically stimulate either the thalamus or subthalamic nucleus

Kaplitt, who hopes to have a full-scale clinical trial for the gene therapy approach underway by year-end, says there are several "inherent advantages" to this new option. Most notably, there are no wires or batteries in the body that could cause infection, it avoids the risks of putting a new electrical source in the brain, and the pacemaker has to be tuned frequently, whereas the gene, according to animal studies, should remain effective for several years.

"If I had these two therapies side by side," Kaplitt says, "I and most of my patients would choose the gene therapy approach."